title: Transcriptome analysis of HIV-infected peripheral blood monocytes: gene transcripts and networks associated with neurocognitive functioning.
abstract: Immunologic dysfunction, mediated via monocyte activity, has been implicated in the development of HIV-associated neurocognitive disorder (HAND). We hypothesized that transcriptome changes in peripheral blood monocytes relate to neurocognitive functioning in HIV+ individuals, and that such alterations could be useful as biomarkers of worsening HAND.
  
  
  METHODS
  mRNA was isolated from the monocytes of 86 HIV+ adults and analyzed with the Illumina HT-12 v4 Expression BeadChip. Neurocognitive functioning, HAND diagnosis, and other clinical and virologic variables were determined. Data were analyzed using standard expression analysis and weighted gene co-expression network analysis (WGCNA).
  
  
  RESULTS
  Neurocognitive functioning was correlated with multiple gene transcripts in the standard expression analysis. WGCNA identified two nominally significant co-expression modules associated with neurocognitive functioning, which were enriched with genes involved in mitotic processes and translational elongation.
  
  
  CONCLUSIONS
  Multiple modified gene transcripts involved in inflammation, cytoprotection, and neurodegeneration were correlated with neurocognitive functioning. The associations were not strong enough to justify their use as biomarkers of HAND; however, the associations of two co-expression modules with neurocognitive functioning warrant further exploration.
authors.affiliation: Department of Neurology, National Neurological AIDS Bank, David Geffen School of Medicine, University of California, Los Angeles, United States. Electronic address: ajlevine@mednet.ucla.edu.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Levine
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.forename: Eric N
authors.initials: EN
authors.lastname: Miller
authors.forename: Elyse J
authors.initials: EJ
authors.lastname: Singer
authors.forename: Paul
authors.initials: P
authors.lastname: Shapshak
authors.forename: Gayle C
authors.initials: GC
authors.lastname: Baldwin
authors.forename: Otoniel
authors.initials: O
authors.lastname: Martínez-Maza
authors.forename: Mallory D
authors.initials: MD
authors.lastname: Witt
authors.forename: Peter
authors.initials: P
authors.lastname: Langfelder
mesh_terms: D000328:Adult; D000368:Aged; D015704:CD4 Antigens / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology* / Q000821:virology; D003863:Depression / Q000209:etiology / Q000821:virology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000235:genetics; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000473:pathology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D013223:Statistics as Topic
chemical_list: D015704:CD4 Antigens; D012333:RNA, Messenger
keywords: HIV-associated neurocognitive disorder; IL6R; Monocyte; WGCNA; gene expression; transcriptome